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http://vmj.sagepub.com/Vascular Medicine
http://vmj.sagepub.com/content/16/3/191The online version of this article can be found at:
DOI: 10.1177/1358863X10395657
2011 16: 191 originally published online 22 February 2011Vasc MedMichael Czihal and Ulrich Hoffmann
Upper extremity deep venous thrombosis
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Vascular Medicine
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The Author(s) 2011
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DOI: 10.1177/1358863X10395657
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Division of Vascular Medicine, University Hospital Campus City
Center, Munich, Germany
Correspondingauthor:Ulrich Hoffmann
Division of Vascular Medicine
University Hospital Campus City Center
Pettenkoferstrasse 8a
D-80336 Munich
Germany
Email: [email protected]
Upper extremity deep venous thrombosis
Michael Czihal and Ulrich Hoffmann
Abstract
Upper extremity deep venous thrombosis is a serious disease entity which, based on the pathogenesis and in view ofthe individual patients prognosis, must be divided into a primary and a secondary form. Primary upper extremity deepvenous thrombosis is, when related to effort, a rather benign disease with excellent prognosis quoad vitam, carrying onlya minor potential of developing disabling post-thrombotic syndrome. If primary upper extremity deep venous thrombo-sis occurs without any obvious cause, screening for underlying malignancy is recommended. Secondary upper extremitydeep venous thrombosis typically occurs in older patients with severe comorbidities, mainly related to indwelling central
venous catheters and cancer. As a consequence of the underlying diseases, prognosis of secondary upper extremitydeep venous thrombosis is poor. Despite a lack of high-quality validation data, ultrasonography is regarded the rst-lineimaging technique, since it is a non-invasive method without exposure to radiation. In case of a non-diagnostic result ofultrasonography, other imaging modalities such as magnetic resonance imaging and computed tomography may be applied.Regardless of the etiology, the cornerstone of therapy is anticoagulant treatment with low molecular weight heparin orunfractionated heparin and vitamin K antagonists in order to prevent thrombus progression and pulmonary embolism.Owing to a lack of evidence, the optimal duration of anticoagulant treatment remains unclear. The additional benet ofcompression therapy as well as of more aggressive therapeutic approaches such as thrombolysis, angioplasty and surgicaldecompression of the thoracic outlet needs to be investigated in randomized trials.
Keywords
cancer; central venous catheter; Paget-von Schroetter syndrome; thoracic outlet syndrome; upper extremity deep venous
thrombosis
Introduction
Upper extremity deep venous thrombosis refers to throm-
bosis of the brachial, subclavian and/or axillary veins and
accounts for up to 11% of all cases of deep venous throm-
bosis.1 Usually, the thrombotic process involves more than
one venous segment, with the subclavian vein most fre-
quently affected.25 The internal jugular vein, the brachio-
cephalic vein and the basilic vein each are additionally
involved in 2030% of patients with upper extremity deep
venous thrombosis.57
The term upper extremity deep venous thrombosis com-
prises different disease entities on the basis of pathogene-
sis, with considerable differences regarding long-term
sequelae and mortality.2,8 Primary upper extremity deep
venous thrombosis is a rare disease occurring spontane-
ously, without clinically apparent risk factors (idiopathic
thrombosis) or after strenuous exercise (effort thrombosis).
While idiopathic thrombosis gives reason for screening for
occult cancer, effort thrombosis is frequently related to the
thoracic outlet syndrome and typically occurs in young and
physically active individuals. The main complication in the
latter patients, otherwise healthy, is post-thrombotic syn-drome due to impairment of the venous outflow. In contrast
to the primary form, secondary upper extremity deep
venous thrombosis develops in consequence of obvious
underlying causes, mainly cancer and indwelling central
venous catheters. Owing to the increasing use of central
venous catheters in patients with cancer or critical illness,
the incidence of catheter-related thrombosis has increased
in past decades.9 The excessively increased mortality rate in
patients with secondary upper extremity deep venous
thrombosis is related to underlying diseases.10 Moreover, it
has been shown that thrombosis of the arm veins, in par-
ticular secondary upper extremity deep venous thrombosis,
carries a substantial risk of pulmonary embolism.11,12
In this review article, we address the risk factors and clin-
ical characteristics of primary and secondary upper extrem-
ity deep venous thrombosis and discuss the diagnostic
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192 VascularMedicine16(3)
options available to date as well as the current strategies in
treatment and prophylaxis.
Risk factors and pathogenesis
PrimaryupperextremitydeepvenousthrombosisThrombosis of the arm veins without evident predisposing
factors in the patients history is classified as primary upper
extremity deep venous thrombosis and accounts for up to
one-third of all thromboses involving the upper extremi-
ties.2,8,13 Primary upper extremity deep venous thrombosis
includes idiopathic thrombosis and effort thrombosis. The
latter, according to the first describers, also entitled Paget-
von Schroetter syndrome, typically occurs in the dominant
arm after strenuous, repetitive or unusual physical activity,
such as weight lifting, rowing or playing tennis.14,15 The
affected individuals are usually young and otherwise
healthy; the male to female ratio is approximately 2:1.15
Themajor predisposing factor for effort thrombosis is the tho-
racic outlet syndrome, which is characterized by external
compression of the neurovascular bundle at the thoracic out-
let.15,16 Whereas venous thoracic outlet syndrome accounts
for only 23% of all cases with thoracic outlet syndrome, it
is frequently found in patients with primary upper extremity
deep venous thrombosis.17,18 It has been hypothesized that
intermittent and positional vein compression during exer-
cise results in repeated microtrauma of the vessel intima
with consecutive activation of the coagulation cascade.13
Repeated vessel trauma may also lead to perivascular scar
tissue formation with persistent vein compression.8,15,19 In
most of these cases, etiology is believed to be compression
of the subclavian vein due to congenital narrowing of the
space bounded by the clavicle, the first rib, the subclavian
muscle tendon and the costoclavicular ligament.15,16 Whereas
compression of the subclavian vein by the anterior scalene
muscle and constriction of the axillary vein by the pectoralis
minor muscle are more unusual causes, cervical ribs in gen-
eral are not considered to be relevant for the development of
venous thoracic outlet syndrome.15,16,20,21
Medical history of subjects with idiopathic upper extrem-
ity deep venous thrombosis lacks apparent risk factors or
obvious underlying diseases.2,8 However, one small obser-
vational study reported on a high rate (25%) of occult malig-nancies in this subgroup of patients.22 Moreover, albeit the
rate is somewhat lower compared to lower extremity deep
venous thrombosis, inherited or acquired coagulopathies are
found in a substantial number of patients with thrombosis of
the arm veins (e.g. upper extremity deep venous thrombosis
34.2% vs lower extremity deep venous thrombosis 55.3% in
the German MAISTHRO registry).23 The prevalence of
coagulation abnormalities appears to be even higher in
patients with idiopathic thrombosis than in those with effort
thrombosis or catheter-related thrombosis.23,24 In particular,
a higher frequency of upper extremity deep venous throm-
bosis was observed in heterozygote carriers of the factor VLeiden and prothrombin G20210A mutation and in patients
with antithrombin-, protein C- or protein S-deficiency.25,26
However, these findings still are controversially discussed,
since other casecontrol studies did not find consistent
differences in the prevalence of the particular clotting anom-
alies between patients with upper extremity deep venous
thrombosis and controls, except for the prothrombin
G20210A mutation.27,28 Data on the prevalence of antiphos-
pholipid antibodies in upper extremity deep venous throm-
bosis are inconsistent.23,24,26,28 Recently, elevated levels of
several coagulation factors (factor VIII, von Willebrand fac-tor, fibrinogen) were shown to be independently associated
with an increased risk of upper extremity deep venous
thrombosis, as was blood group non-0 compared to 0.29
On the contrary, hyperhomocysteinemia as well as hemor-
heological alterations do not seem to contribute to the
pathogenesis of thrombosis of the arm veins.26,30
Secondaryupperextremitydeepvenousthrombosis
Upper extremity deep venous thrombosis is classified as
secondary in the presence of known endogenous or exoge-
nous risk factors. The secondary form accounts for abouttwo-thirds of all cases with upper extremity deep venous
thrombosis and usually affects older patients with severe
comorbidities.2,8,13
The most important risk factor for upper extremity deep
venous thrombosis is the presence of an indwelling central
venous catheter.1,25 Owing to the increased use of central
venous catheters for administration of medication, blood
products and parenteral nutrition as well as for hemodialysis,
the incidence of catheter-related thrombosis has increased in
past decades, and today a central venous catheter is present
in at least every second patient with thrombosis of the arm
veins.8,10,31 Dependent on the catheters entry site, the inter-
nal jugular vein is also frequently affected. However,
whether the subclavian or the internal jugular vein are cho-
sen for vascular access does not seem to affect the risk of
thrombosis.9 The risk of developing catheter-related throm-
bosis rather depends on an individual patients profile and on
factors related to the catheter itself. Cancer patients with ind-
welling central venous catheters are at particular risk, with
rates of thrombosis detected by screening venography rang-
ing from 16% to 66%.32,33 In line with these figures, an ultra-
sonographic screening study in patients with hematological
disorders and indwelling central venous catheters reported a
cumulative incidence of catheter-related thrombosis of
29%.34 A high frequency of upper extremity deep venousthrombosis (23%) was also observed in patients who under-
went implantation of permanent pacemaker leads.35 Inherited
coagulation disorders (the factor V Leiden and prothrombin
G20210A mutation) seem to result in a threefold increased
risk of developing catheter-associated thrombosis.36
Catheter-related factors that have been reported to increase
the risk of thrombosis include the type and material of the
catheter, position of the catheter tip, catheter infection and a
history of prior central venous catheterization (Table 1).9,33,3641
Whether an ultrasound guided-insertion technique reduces
the risk of thrombosis, when compared to a landmark-guided
technique, is currently not known.Malignancy is the other main risk factor for secondary
upper extremity deep venous thrombosis. Even though the
thrombotic risk in cancer patients mainly results from
indwelling central venous catheters, active malignancy in
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CzihalMandHoffmannU 193
patients without central venous catheters in the MEGA study
resulted in an 18-fold increased risk of upper extremity deep
venous thrombosis.25 In large cohort studies, 2238% of the
patients with thrombosis of the arm veins had cancer.1,10,25,31,42
The thrombotic process is thought to be multifactorial, with
endothelial damage caused by indwelling catheters or radio-
therapy, venous stasis due to immobilization or direct vein
compression by the tumor itself, and cancer-induced inhibi-
tion of natural anticoagulants and fibrinolysis as well as
release of prothrombotic factors.9,43 Of note, the risk of
developing deep venous thrombosis increases in the pres-
ence of distant metastases.25,33 It has been suggested that, at
least in the presence of an indwelling catheter, ovarian carci-
noma and lung adenocarcinoma could carry a particularly
increased risk of upper extremity deep venous thrombosis,when compared with other malignant entities.9,39,41 In addi-
tion, cancer treatment also affects the risk of venous throm-
boembolism. This has been shown particularly for the use of
antiangiogenesis agents, such as thalidomide or bevacizu-
mab.44 Furthermore, administration of erythropoiesis-stimu-
lating agents is associated with an increased rate of venous
thromboembolic events in cancer patients.45 However, spe-
cific data on the risk of upper extremity deep venous throm-
bosis related to cancer treatment are not available.9
Another evident risk factor for thrombosis of the arm
veins is upper extremity immobilization by plaster casts or
following arm surgery.25
Previous episodes of lower extrem-ity deep venous thrombosis are found in 18% of these cases,
and a history of lower extremity deep venous thrombosis or
a family history of venous thromboembolism also increase
the risk of upper extremity deep venous thrombosis.3,25 The
association between oral contraceptive use and the develop-
ment of upper extremity deep venous thrombosis is still con-
troversial, but women taking oral contraceptives and
carrying the factor V Leiden or prothrombin G20210A
mutation appear to be at particular risk.3,25,26,28 On the con-
trary, obesity and postmenopausal hormone replacement
therapy do not seem to increase the risk.25,46 While the gen-
eral risk of upper extremity deep venous thrombosis related
to pregnancy has not been assessed, some case reports raised
concerns about thrombosis of the arm veins (and more fre-
quently the internal jugular veins) related to ovarian hyper-
stimulation syndrome, a serious complication of in vitro
fertilization.47 In this group of patients, the site specificity
may be explained by excessively elevated estrogen levels in
the peritoneal fluid, which is drained via the thoracic andright lymphatic duct into the upper extremity veins with
consecutive local activation of the coagulation cascade.48
The main risk factors for upper extremity deep venous
thrombosis are summarized in Figure 1.
Clinical presentation
Signsandsymptomsofupperextremitydeepvenousthrombosis
Patients suffering from upper extremity deep venous throm-
bosis most commonly present with edematous swelling ofthe affected arm and/or upper extremity discomfort or pain.1,3
Other clinical features such as cyanosis, visible collateral
veins at the shoulder girdle (Figure 2) or jugular distension
are less frequently found.49 Of note, most thrombotic events
Table 1. Catheter characteristics associated with an increased
risk of upper extremity deep venous thrombosis9,33,3641
Left insertion sideMore than one insertion attemptCatheter tip localized proximal to the atriocaval junctionCatheter material (polyethylene, polyvinylchloride > silicon,polyurethane)Number of lumina (triple lumen > double lumen)Prior catheterization at the same puncture siteProlonged catheter dwell time (> 2 weeks)Catheter-related infection/septicemia
Table 2. Clinical probability score for upper extremity deep
venous thrombosis59
Indwelling venous catheter 1 pointLocalized pain 1 pointUnilateral pitting edema 1 pointOther diagnosis at least as plausible 1 point 0 low clinical probability (rate of thrombosis: 13%)1 intermediate clinical probability (rate of thrombosis: 38%) 2 high clinical probability (rate of thrombosis: 69%)
Figure 1. Etiology of upper extremity deep venous thrombosis.
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194 VascularMedicine16(3)
related to indwelling central venous catheters remain com-pletely subclinical and may only be discovered during the
diagnostic workup of catheter sepsis, catheter dysfunction
with an inability to draw blood from the catheter, or pulmo-
nary embolism.34,50 Low-grade fever may be caused by
venous thromboembolism, but can also be the heralding sign
of underlying malignancy. Higher fever occurs with catheter
sepsis or septic thrombophlebitis.8 Simultaneous occurrence
of bilateral upper extremity deep venous thrombosis is a typ-
ical feature of cancer-associated venous thromboembolism.10
Signsandsymptomsofunderlyingthoracic
outletsyndromeUnderlying thoracic outlet obstruction is mostly asympto-
matic prior to effort thrombosis. If clinically apparent, the
thoracic outlet syndrome usually (more than 90%) presents
with neurological symptoms due to compression of the bra-
chial plexus and is characterized by arm pain or paresthesia
radiating to the fourth and fifth digit, worsening with hyper-
abduction of the shoulder.21 Symptoms related to thoracic
outlet obstruction with venous compression are rare, typi-
cally presenting with position-dependent arm swelling and
cyanosis.16,17 A careful medical history and clinical examina-
tion are essential for diagnosis of the thoracic outlet syn-drome. Several clinical provocative tests such as the
military-exercise test (Edens test) and the hyperabduction
test (Wrights maneuver) are described in the literature.
Edens test is applied for diagnosis of costoclavicular com-
pression: the patient is asked to breathe in and to retract his/
her shoulders, while the examiner draws the patients arm
down. Wrights maneuver (retraction of the hyperabducted,
externally rotated arm) is useful for the detection of costo-
pectoral compression. However, although frequently used
for the evaluation of suspected thoracic outlet obstruction,
diagnostic accuracy of provocative maneuvers is unclear as
a diagnostic gold standard is missing and, on average, sensi-tivity (73%) and specificity (53%) are low.17 Moreover,
positive results are only indirectly indicated by the onset of
neurological symptoms, pulse attenuation or a subclavian
artery bruit.17 In the majority of cases with suspected venous
thoracic outlet syndrome, subclavian vein compression can-
not be directly disclosed. It must be pointed out in this con-
text, that Adsons maneuver appears to be of little value in
suspected venous thoracic outlet syndrome, since it aims to
detect compression within the interscalene triangle, where
only the brachial nerve and the subclavian artery run.
In view of these limitations, additional dynamic testing
with indirect (pulse volume recording) and direct (ultra-
sonography, magnetic resonance imaging, contrast venog-
raphy) assessment of compression of the vascular structures
at the thoracic outlet during postural maneuvers may be
helpful to further establish the diagnosis of venous tho-
racic outlet syndrome (Figure 3).16,17 Of note, confirmation
Figure 2. Dilatation of subcutaneous collateral veins in apatient with left-sided upper extremity deep venous thrombosis.
Figure 3. Non-occluding thrombus of the right subclavian vein with prominent collateral veins in a patient with effort thrombosis(A). Hyperabduction leads to complete venous compression with a stop in venous blood flow (B).
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CzihalMandHoffmannU 195
of venous compression does not necessarily imply a
clinically relevant syndrome since this phenomenon is also
frequently observed in asymptomatic individuals during
arm elevation.51
Complications
Post-thromboticsyndrome
The post-thrombotic syndrome is a chronic complication of
upper extremity deep venous thrombosis, leading to signifi-
cant functional disability and impaired quality of life, in par-
ticular when occurring in the dominant arm.52 There is
currently no accepted diagnostic standard available for the
diagnosis of this disorder. Depending on the criteria applied,
frequencies of post-thrombotic syndrome vary considerably,
ranging from 7% to 46%.53 The post-thrombotic syndrome
seems to occur less frequently after catheter-associated
thrombosis.52
Noteworthy, there is no clear correlationbetween morphologic and hemodynamic sequelae and devel-
opment of the post-thrombotic syndrome.5,7,54 Symptoms
include edema, persistent pain or heaviness of the affected
arm, limb fatigue with exertion, skin discoloration and dis-
tended collateral veins in the shoulder region. Severe post-
thrombotic syndrome resulting in skin ulceration is virtually
unknown after upper extremity deep venous thrombosis.5,52,55
Recurrentupperextremitydeepvenousthrombosis
The 2-year cumulative incidence rates of recurrent venous
thromboembolism after a first episode of upper extremity
deep venous thrombosis range between 4% and 8%.10,26,42,55
Thus, the overall recurrence rates after deep venous throm-
bosis of the upper and lower extremities appear to be simi-
lar, while patients with idiopathic thrombosis of the arm
veins exhibit a significantly lower risk of recurrence when
compared to subjects with idiopathic lower extremity deep
venous thrombosis.4,10 Upper extremity deep venous throm-
bosis associated with an indwelling catheter goes along
with a decreased risk of recurrent thromboembolic events.
On the other hand, once a catheter is removed after a
thrombotic event there is a high probability (up to 86%) of
recurrent thrombosis at the insertion side of a new cathe-
ter.56 Patients with cancer and women could be at higherrisk for recurrence.10,42 In a longitudinal study by Martinelli
and co-workers, the presence of thrombophilia was not
associated with a significant increase in the risk of recur-
rent thrombosis.26 Another cohort study failed to document
an association between the number of recurrent events of
upper extremity deep venous thrombosis and the presence
of the factor V Leiden or prothrombin G20210A mutation.42
Pulmonaryembolism
The actual incidence of pulmonary embolism resulting
from upper extremity deep venous thrombosis is difficult toascertain, as the studies reporting on this complication dif-
fer with regard to their design (retrospective vs prospec-
tive), the patient population investigated (percentage of
patients with effort-related, idiopathic or secondary throm-
bosis) and the criteria applied for diagnosis of pulmonary
embolism (symptomatic event vs routine screening). Most
clinical observations reported rates of symptomatic pulmo-
nary embolism between 3% and 12%.1,3,4,8,10,12,31,55 This
number is considerably lower compared to the frequency of
clinically overt pulmonary embolism in lower extremitydeep venous thrombosis, which was between 16% and 29%
in large registries.1,10 Prandoni et al. revealed pulmonary
embolism using routine perfusion-scintigraphy in as much
as 8 of 22 prospectively evaluated patients (36%) with
thrombosis of the arm veins.3 In earlier studies using
screening scintigraphy, Monreal and co-workers docu-
mented pulmonary embolism in 13% and 16% of patients
with upper extremity deep venous thrombosis, respec-
tively.11,57 Carriers of central venous catheters suffering
from upper extremity deep venous thrombosis appear to be
at particular risk of developing pulmonary embolism,
whereas in primary thrombosis of the arm veins (parti-cularly in effort thrombosis) pulmonary embolism seems
to be a rare complication.11,12 Symptoms of pulmonary
embolism include dyspnoea, visceral or pleuritic chest
pain, syncope, low-grade fever and sinus tachycardia. Sinus
tachycardia may also occur due to obstruction of the supe-
rior vena cava, a potentially life-threatening condition
going along with facial edema, vertigo, vision disturbances
and dyspnoea.1 Fatal pulmonary embolism is an extremely
rare event under therapeutic anticoagulation.13,10,31,57
Mortality
A striking difference exists between primary and secondary
upper extremity deep venous thrombosis regarding the
prognosis quoad vitam. Patients with primary (effort-
related) thrombosis are typically young and otherwise
healthy, whereas subjects with secondary thrombosis of the
arm veins are frequently of advanced age and/or troubled
by chronic medical conditions. Hence, this latter group has
a considerably worse outcome, with cancer being the major
cause of death.42,58 In the RIETE Registry, the overall
3-month mortality rate of patients with upper extremity
deep venous thrombosis was 11%, a percentage signifi-
cantly higher compared to that of patients with lower
extremity deep venous thrombosis, of whom 7% haddied within 3 months after diagnosis. The subgroup of
patients with known malignancy had a very poor prognosis,
with a death rate reaching from 16% in cancer patients with
catheter-related thrombosis to 28% in cancer patients with-
out an indwelling central venous catheter (Figure 4).10
Hingorani et al. also observed an excessive mortality rate of
28% after 2 months in their cohort of patients with upper
extremity deep venous thrombosis. They found that the
presence of a central venous catheter, concomitant lower
extremity deep venous thrombosis, not undergoing antico-
agulation and the placement of a superior vena cava filter
were associated with an increased short-term mortality.31
Other cohort studies reported on mortality rates between
21% and 50% in patients with thrombosis of the arm veins
after a mean follow-up of between 2 and 4 years.42,55,58
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196 VascularMedicine16(3)
Diagnostic strategies
ClinicalpredictionscoreandD-dimertest
The clinical signs and symptoms of upper extremity deep
venous thrombosis are non-specific. Alternative diagnoses
include thrombophlebitis, cellulitis, venous congestion due
to external vessel compression and lymphatic edema.3
Constans and colleagues proposed a clinical probability
score for upper extremity deep venous thrombosis consi-
sting of four items and yielding a sensitivity of 78% and
a specificity of 64% (Table 2).59 However, in the group
with the low clinical probability still 13% of patients subse-
quently were diagnosed with thrombosis of the arm
veins.59,60 Therefore, objective diagnostic testing to confirm
or exclude upper extremity deep venous thrombosis is
mandatory.2,3,8,9
Unlike in deep venous thrombosis of the lower limbs,
diagnostic algorithms based on clinical probability and sub-
sequent D-dimer or ultrasound testing have not been evalu-
ated in upper extremity deep venous thrombosis. So far,
there is only one small study reporting on the diagnostic
accuracy of the D-dimer test in patients suspected of having
thrombosis of the arm veins. Compared with ultrasonogra-
phy in 52 patients (23 patients with cancer, 18 patients with
an indwelling central venous catheter), the test showed asensitivity of 100% but a specificity as low as 14%, result-
ing in positive and negative predictive values of 32% and
100%, respectively.61 Given the high prevalence of cancer
and critical illness among in-hospital patients with upper
extremity deep venous thrombosis, D-dimer testing in these
patients seems to be of limited value for the diagnostic
workup. By contrast, a diagnostic algorithm including
D-dimer testing may be more efficient in outpatients with
suspected primary thrombosis of the arm veins, as most of
these patients do not have relevant comorbidities.9,60,61
Ultrasonography
Ultrasonography has replaced other non-invasive meth-
ods such as strain-gauge plethysmography, which only
indirectly assess venous patency. A complete examination
should include compression sonography (transverse plain)
of the internal jugular vein, the brachial and axillary vein,
and the subclavian vein distal to the clavicle. The cephalic
vein and the basilic vein at their confluence with the deep
venous system should also be visualized. Thrombosis is
characterized by incomplete compressibility of the venous
segment examined. Although the additional diagnostic ben-
efit is questionable,3,60 evaluation of the proximal subcla-
vian veins and the brachiocephalic veins on both sides by
pulsed wave- and color Doppler ultrasonography may be
helpful to assess venous patency. Examination of these cen-
trally situated venous segments requires a supraclavicular
approach and may necessitate the use of a phased array
transducer. Unilateral conversion of the normal biphasic
flow pattern into a non-pulsatile, continuous flow signal
suggests central venous obstruction as an indirect sign of
proximal thrombosis of the arm veins (Figure 5).62,63 Once
a catheter is removed after catheter-induced thrombosis, it
is reasonable to perform another ultrasound to establish a
new baseline.
A recent systematic review reported a sensitivity of 97%
and a specificity of 96% for the diagnosis of upper extrem-
ity deep venous thrombosis with compression-ultrasonog-
raphy.60 However, sufficient high-quality validation data is
still missing because of small sample sizes and/or methodo-logical shortcomings of the studies available.3,60,64,65 Despite
these limitations, ultrasonography today is regarded the
first-line diagnostic imaging procedure in suspected upper
extremity deep venous thrombosis, since it is a non-inva-
sive and inexpensive method without exposure to radiation.
Interobserver agreement can be considered to be high in
experienced centers.3 However, the safety of withholding
anticoagulation therapy in symptomatic patients with a
negative ultrasonography study still remains uncertain.3,65
There are also no data on the value of diagnostic algorithms
including serial sonographic examinations or the combina-
tion of pretest probability and a single sonographic study.In case of central venous obstruction or a non-diagnostic
ultrasonography in subjects with high clinical suspicion
(e.g. in patients with indwelling central venous catheters),
additional imaging techniques are required.2,9,60
Figure 4. Three-month mortality rate of upper extremity deep venous thrombosis according to data from the RIETE-registry.10
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Otherimagingtechniques
Only preliminary data are available regarding the diagnostic
value of magnetic resonance- and computed tomography
venography.60 Potential advantages include the visualization
of the central thoracic veins as well as collateral pathways
and the confirmation of alternative diagnoses, in particular
vein compression caused by local tumor growth.2,8,9 In two
cohort studies, magnetic resonance imaging (time-of-flight
magnetic resonance venography on a 1-Tesla unit in one
study, three-dimensional gadolinium-enhanced magnetic
resonance venography on a 1.5-Tesla unit in another study)
was compared with other imaging modalities (contrast
venography and ultrasonography) in some of the patients
investigated. The results were promising, showing a high
diagnostic accuracy and even an additional benefit of mag-
netic resonance venography in determining the thrombus
extent.66,67 On the contrary, Baarslag et al. reported a sensi-
tivity and specificity of magnetic resonance venography
(1.5-Tesla unit) compared with contrast venography of only
71% and 89% (time-of-flight) and 50% and 80% (three-
dimensional gadolinium-enhanced magnetic resonance
venography), respectively. Furthermore, the authors notedthat for several reasons (e.g. pacemaker, claustrophobia)
magnetic resonance imaging was not feasible in one-third of
the patients.68 Newer studies utilizing advanced magnetic
resonance imaging-techniques are lacking. Surprisingly, the
value of computed tomography venography for diagnosis of
upper extremity deep venous thrombosis so far has not been
systematically evaluated. To date, magnetic resonance
imaging and computed tomography should be considered as
supplemental methods to be applied in case of unequivocal
or negative results of ultrasonography despite high clinical
suspicion. Further evidence is needed to clearly establish the
diagnostic benefit of both imaging modalities.Although still considered the diagnostic reference stand-
ard, contrast venography today is only exceptionally per-
formed in suspected upper extremity deep venous thrombosis
because of its inherited methodological drawbacks, including
the invasive character and the need for application of iodi-
nated contrast agents and exposure to radiation. The advan-
tages of the method are the ability to visualize the entire deep
venous system and to delineate functional vein compression
as well as the collateral circulation (Figure 3).8,69
Screeningforthrombophiliaandoccultcancer
According to results from large registries, hypercoaguable
states seem to be a rather frequent finding in upper extremity
deep venous thrombosis.23 As stated above, there is currently
no evidence for an association between the presence of
thrombophilic factors and an increased recurrence rate after
a first episode of thrombosis of the arm veins.26,42 As the vast
majority of thrombotic episodes are causally related to stren-
uous effort, cancer or indwelling central venous catheters,
regular screening for thrombophilia will only rarely affect
clinical management. Moreover, as the overall risk of recur-
rence is low and data regarding the benefit of a prolonged
anticoagulation are lacking, there is currently no scientific
basis to recommend general screening for thrombophilia in
upper extremity deep venous thrombosis.70 From a clinical
perspective, screening for the factor V Leiden and pro-thrombin G20210A mutation and for antithrombin-, protein
C- or protein S-deficiency might be advisable in patients
with a positive family history of venous thromboembolism
and in the small group of patients with otherwise unexplained
upper extremity deep venous thrombosis.2,23 Based on the
documented benefit of long-term anticoagulation in patients
with the antiphospholipid syndrome and venous thromboem-
bolism, screening for lupus anticoagulants and anticardioli-
pin/anti-2-glycoprotein antibodies may also be considered
in selected patients with upper extremity deep venous throm-
bosis (e.g. subjects with concomitant arterial thrombosis and
women with a history of recurrent pregnancy loss).71,72
In view of the potential risk of underlying occult malig-
nancies, patients with unexplained upper extremity deep
venous thrombosis should undergo cancer screening.22
Screening should be performed in accordance with the
Figure 5. Side difference of the venous flow in the distal subclavian vein in a patient with thrombosis of the proximal rightsubclavian vein. (A) Normal biphasic flow pattern; (B) continuous flow signal.
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198 VascularMedicine16(3)
recommendations for patients with lower extremity deep
venous thrombosis, including a detailed medical history
and physical examination, routine laboratory analysis,
abdominal ultrasound, chest X-ray and completion of the
age- and sex-specific screening measures. It should be
pointed out that it is unknown whether screening for malig-
nant conditions in patients with venous thromboembolism,aimed to detect early and limited disease stages, will reduce
cancer-related mortality and morbidity.73
Treatment and prophylaxis
Anticoagulanttreatment
Although it is generally accepted that, as for patients with
lower extremity deep venous thrombosis, patients with
(symptomatic) thrombosis of the arm veins require antico-
agulant treatment to prevent thrombus propagation and pul-
monary embolism, the optimal treatment duration andintensity so far was not determined in randomized control-
led trials. Therefore, the management of patients with both
primary and secondary thrombosis remains controversial.2
Based on the available data from prospective cohort stud-
ies,26,55,74,75 the current guidelines recommend initial treat-
ment with low molecular weight heparin (LMWH) or
unfractionated heparin, followed by vitamin K antagonists
(target INR: range 2.03.0 for at least 3 months).76 Even in
the presence of severe comorbidities, outpatient treatment
may be feasible in many patients.70
The necessity to remove a central venous catheter in
catheter-related thrombosis depends on the ongoing need
for a vascular access. If the device is functional and further
required for the patients care, it can be left on site.9,50,75,76 If
so, it is recommended to continue anticoagulation as long
as the catheter remains in place. Therapeutic anticoagula-
tion should not be shortened to fewer than 3 months after
catheter removal.76 The treatment of patients with active
malignancy suffering from upper extremity deep venous
thrombosis is particularly challenging, as these patients
have an increased risk of recurrence but also an increased
incidence of major bleeding complications under anticoag-
ulation.10 In patients with venous thromboembolism and
cancer, anticoagulation is recommended for at least 36
months.9 Since there are no data for the time period beyond6 months, indication for treatment continuation thereafter
depends on the tumor activity and the individual bleeding
risk. On the basis of data on cancer-associated lower
extremity deep venous thrombosis, indicating a lower
recurrence risk but similar bleeding risk, the use of LMWH
may be preferred over vitamin K antagonists also in pati-
ents with upper extremity deep venous thrombosis.9,77,78
However, there are no specific data available regarding the
use of LMWH or newer anticoagulants for the long-term
treatment of upper extremity deep venous thrombosis.76
While there is no evidence to support indefinite antico-
agulant therapy for a first unprovoked episode, this treat-ment regimen may be considered in recurrent upper
extremity deep venous thrombosis.9,76
Thrombolysis,surgicalandinterventionalmethods
Thrombolysis aims to early restore venous patency, prima-
rily to reduce the risk of post-thrombotic syndrome.8
Thrombolysis may theoretically reduce the rate of throm-
boembolic recurrences or the need for long-term anticoagu-
lation, although there are no data available to support thishypothesis. A large number of mainly retrospective studies
have reported encouraging results of thrombolytic therapy
alone or in combination with surgical decompression and/
or percutaneous transluminal angioplasty with or without
stenting of the subclavian vein for restoration of venous
patency in upper extremity deep venous thrombosis.15,76,79
In cases with upper extremity deep venous thrombosis
associated with acute thrombotic superior vena cava
obstruction, thrombolytic therapy eventually supported by
angioplasty and stenting of the superior vena cava may
even be life-saving.8 Various protocols with streptokinase,
urokinase and recombinant tissue plasminogen activator indifferent doses and with different methods of administra-
tion (intravenous, catheter-directed) have been applied,
mostly in patients with primary thrombosis of the arm
veins.15,76,79 However, randomized studies comparing
thrombolysis with anticoagulation alone for the initial treat-
ment of upper extremity deep venous thrombosis are lack-
ing. Since severe post-thrombotic syndrome is almost never
observed after conservative treatment of upper extremity
deep venous thrombosis, it remains unclear to what extent
patients may benefit from thrombolysis in the long-term.5,52
According to the current guidelines, thrombolytic therapy
may be considered in selected patients with acute thrombo-
sis of the arm veins and severe symptoms but low bleeding
risk.76
Based on single-center series, some authors recommend
a multimodal approach combining thrombolysis, angi-
oplasty with or without stent placement and early or late
surgical decompression of the thoracic outlet for the treat-
ment of primary upper extremity deep venous thrombo-
sis.15,79 Surgical decompression usually involves resection
of parts of the clavicle and the first rib, supplemented by
circumferential venolysis and scalenectomy, if appropri-
ate.8,15,19 As for thrombolysis alone, randomized studies
comparing a multimodal therapeutic approach to conser-
vative treatment with anticoagulation alone are lackingand uncertainty exists regarding the long-term benefit.76
According to the guidelines, surgical decompression may
be considered in symptomatic patients with failure of med-
ical treatment and confirmation of venous compression at
the thoracic outlet.76 Venous bypass grafting is generally
not recommended as grafts may frequently fail because of
low venous pressure and flow.8,76
Placement of superior vena cava filters may only be con-
sidered in patients with contraindications for anticoagulant
treatment and pulmonary embolism.76 The potential benefit
must be outweighed against the significant risks of filter
placement, including filter dislocation and development ofthe superior vena cava syndrome due to thrombus forma-
tion in the filter.2,8
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A high level of evidence from randomized studies exists
for low-dose thrombolytic treatment of catheter-dysfunction
due to thrombotic luminal occlusion.9,50 For example, cathe-
ter function was restored in 74% of the patients treated with
recombinant tissue plasminogen activator (2 mg per 2 ml)
compared to 17% of patients in the placebo arm in a study by
Ponec et al. The associated bleeding risk was negligible.80
Compressiontherapy
The effectiveness of compression therapy in order to pre-
vent the post-thrombotic syndrome after thrombosis of the
arm veins is unclear and this treatment modality hence is
not generally recommended by the current guidelines.52,76
The use of elastic bandages or elastic compression sleeves
is suggested only for patients with persistent symptoms of
the post-thrombotic syndrome.76
PreventionofupperextremitydeepvenousthrombosisDespite data available from several randomized studies,
controversies remain regarding the value of thrombopro-
phylaxis in cancer patients with indwelling central venous
catheters.9,50 By contrast with results from previous pro-
spective studies, more recent large-scale randomized trials
did not show a significant benefit of the prophylactic use of
either low-dose warfarin (1 mg once daily) or LMWH in
this patient population.8184 In accordance with the results of
various meta-analyses, the current guidelines of the
American College of Chest Physicians therefore recom-
mend against the use of LMWHs or vitamin K antagonists
to prevent upper extremity deep venous thrombosis in can-
cer patients with indwelling central venous catheters.8588
This recommendation also applies for critically ill patients
with indwelling catheters not suffering from cancer, since
for this group of patients no clear benefit of anticoagulant
prophylaxis was observed in small randomized studies.50
Conclusion
Primary upper extremity deep venous thrombosis occurs
either idiopathically or is effort-related. Occult malignancy
is a frequent underlying cause of idiopathic thrombosis,whereas effort-related thrombosis (Paget-von Schroetter
syndrome) results from venous obstruction at the thoracic
outlet. The main causes for secondary upper extremity deep
venous thrombosis are central venous catheters and malig-
nancies, with cancer being the major factor for the exces-
sive mortality rate in these patients. Diagnosis of thrombosis
of the arm veins is based on imaging methods, primarily
ultrasonography. The cornerstone of treatment in all
patients with upper extremity deep venous thrombosis is
anticoagulation with LMWH and vitamin K antagonists in
order to prevent thrombus progression and pulmonary
embolism. The benefit of other treatment modalities, suchas compression therapy, thrombolysis and surgical decom-
pression, needs to be investigated in randomized trials.
Acknowledgement
The authors declare that they have no conflicts of interest.
Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.
References
1. Joffe HV, Kucher N, Tapson VF, Goldhaber SZ. Upper-
extremity deep vein thrombosis: a prospective registry of
592 patients. Circulation 2004; 110: 16051611.
2. Bernardi E, Pesavento R, Prandoni P. Upper extremity
deep venous thrombosis. Semin Thromb Hemost 2006; 32:
729736.
3. Prandoni P, Polistena P, Bernardi E, et al. Upper-extremity
deep vein thrombosis. Risk factors, diagnosis, and complica-
tions.Arch Intern Med1997; 157: 5762.
4. Lechner D, Wiener C, Weltermann A, Eischer L, Eichinger S,
Kyrle PA. Comparison between idiopathic deep veinthrombosis of the upper and lower extremity regarding
risk factors and recurrence. J Thromb Haemost2008; 6:
12691274.
5. Persson LM, Arnhjort T, Larfars G, Rosfors S. Hemodynamic
and morphologic evaluation of sequelae of primary upper
extremity deep venous thromboses treated with anticoagula-
tion.J Vasc Surg2006; 43: 12301235.
6. Ascher E, Salles-Cunha S, Hingorani A. Morbidity and mor-
tality associated with internal jugular vein thromboses. Vasc
Endovasc Surg2005; 39: 335339.
7. Heron E, Lozinguez O, Emmerich J, Laurian C, Fiessinger
JN. Long-term sequelae of spontaneous axillary-subclavian
venous thrombosis.Ann Intern Med1999; 131: 510513.
8. Joffe HV, Goldhaber SZ. Upper-extremity deep vein throm-
bosis. Circulation 2002; 106: 18741880.
9. Shivakumar SP, Anderson DR, Couban S. Catheter-
associated thrombosis in patients with malignancy. J Clin
Oncol2009; 27: 48584864.
10. Munoz FJ, Mismetti P, Poggio R, et al. Clinical outcome of
patients with upper-extremity deep vein thrombosis: results
from the RIETE Registry. Chest2008; 133: 143148.
11. Monreal M, Lafoz E, Ruiz J, Valls R, Alastrue A. Upper-
extremity deep venous thrombosis and pulmonary embolism.
A prospective study. Chest1991; 99: 280283.
12. Kooij JD, van der Zant FM, van Beek EJ, Reekers JA.Pulmonary embolism in deep venous thrombosis of the
upper extremity: more often in catheter-related thrombosis.
Neth J Med1997; 50: 238242.
13. Flinterman LE, Van Der Meer FJ, Rosendaal FR, Doggen
CJ. Current perspective of venous thrombosis in the upper
extremity.J Thromb Haemost2008; 6: 12621266.
14. Van Stralen KJ, Blom JW, Doggen CJ, Rosendaal FR.
Strenuous sport activities involving the upper extremities
increase the risk of venous thrombosis of the arm.J Thromb
Haemost2005; 3: 21102111.
15. Illig KA, Doyle AJ. Paget-Schroetter syndrome: a compre-
hensive review.J Vasc Surg2010; 51: 15381547.16. Sanders RJ, Hammond SL. Venous thoracic outlet syndrome.
Hand Clin 2004; 20: 113118, viii.
at Cairo University on September 6, 2011vmj.sagepub.comDownloaded from
http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/8/3/2019 Upper Extremity Deep Venous Thrombosis (2)
11/13
200 VascularMedicine16(3)
17. Vanti C, Natalini L, Romeo A, Tosarelli D, Pillastrini P.
Conservative treatment of thoracic outlet syndrome. A
review of the literature.Eura Medicophys 2007; 43: 5570.
18. Gloviczki P, Kazmier FJ, Hollier LH. Axillary-subclavian
venous occlusion: the morbidity of a nonlethal disease.
J Vasc Surg1986; 4: 333337.
19. Thompson RW, Schneider PA, Nelken NA, Skioldebrand
CG, Stoney RJ. Circumferential venolysis and paraclavicular
thoracic outlet decompression for effort thrombosis of the
subclavian vein.J Vasc Surg1992; 16: 723732.
20. Sanders RJ, Rao NM. Pectoralis minor obstruction of the
axillary vein: report of six patients. J Vasc Surg2007; 45:
12061211.
21. Jamieson CW. Venous complications of the thoracic outlet
syndrome.Eur J Vasc Surg1987; 1: 13.
22. Girolami A, Prandoni P, Zanon E, Bagatella P, Girolami B.
Venous thromboses of upper limbs are more frequently asso-
ciated with occult cancer as compared with those of lower
limbs.Blood Coagul Fibrinolysis 1999; 10: 455457.23. Linnemann B, Meister F, Schwonberg J, Schindewolf M,
Zgouras D, Lindhoff-Last E. Hereditary and acquired throm-
bophilia in patients with upper extremity deep-vein thrombo-
sis. Results from the MAISTHRO registry. Thromb Haemost
2008; 100: 440446.
24. Heron E, Lozinguez O, Alhenc-Gelas M, Emmerich J,
Fiessinger JN. Hypercoagulable states in primary upper-
extremity deep vein thrombosis.Arch Intern Med2000; 160:
382386.
25. Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Old and new
risk factors for upper extremity deep venous thrombosis.
J Thromb Haemost2005; 3: 24712478.
26. Martinelli I, Battaglioli T, Bucciarelli P, Passamonti SM,
Mannucci PM. Risk factors and recurrence rate of primary
deep vein thrombosis of the upper extremities. Circulation
2004; 110: 566570.
27. Bombeli T, Basic A, Fehr J. Prevalence of hereditary throm-
bophilia in patients with thrombosis in different venous sys-
tems.Am J Hematol2002; 70: 126132.
28. Vaya A, Mira Y, Mateo J, et al. Prothrombin G20210A muta-
tion and oral contraceptive use increase upper-extremity deep
vein thrombotic risk. Thromb Haemost2003; 89: 452457.
29. Flinterman LE, van Hylckama Vlieg A, Rosendaal FR,
Doggen CJ. Venous thrombosis of the upper extremity: effect
of blood group and coagulation factor levels on risk. Br JHaematol2010; 149: 118123.
30. Vaya A, Martinez TM, Romagnoli M, Lopez M, Ricart A,
Corella D. Lack of association between hemorheological
alterations and upper-extremity deep vein thrombosis. Clin
Hemorheol Microcirc 2009; 41: 279285.
31. Hingorani A, Ascher E, Markevich N, et al. Risk factors for
mortality in patients with upper extremity and internal jugu-
lar deep venous thrombosis.J Vasc Surg2005; 41: 476478.
32. Verso M, Agnelli G. Venous thromboembolism associated
with long-term use of central venous catheters in cancer
patients.J Clin Oncol2003; 21: 36653675.
33. Verso M, Agnelli G, Kamphuisen PW, et al. Risk factors forupper limb deep vein thrombosis associated with the use of
central vein catheter in cancer patients. Intern Emerg Med
2008; 3: 117122.
34. Van Rooden CJ, Rosendaal FR, Barge RM, et al. Central
venous catheter related thrombosis in haematology patients
and prediction of risk by screening with Doppler-ultrasound.
Br J Haematol2003; 123: 507512.
35. Van Rooden CJ, Molhoek SG, Rosendaal FR, Schalij MJ,
Meinders AE, Huisman MV. Incidence and risk factors of early
venous thrombosis associated with permanent pacemaker
leads.J Cardiovasc Electrophysiol2004; 15: 12581262.
36. Van Rooden CJ, Rosendaal FR, Meinders AE, Van Oostayen
JA, Van Der Meer FJ, Huisman MV. The contribution of
factor V Leiden and prothrombin G20210A mutation to
the risk of central venous catheter-related thrombosis.
Haematologica 2004; 89: 201206.
37. Van Rooden CJ, Schippers EF, Barge RM, et al. Infectious
complications of central venous catheters increase the risk
of catheter-related thrombosis in hematology patients: a pro-
spective study.J Clin Oncol2005; 23: 26552660.
38. Raad II, Luna M, Khalil SA, Costerton JW, Lam C, Bodey
GP. The relationship between the thrombotic and infectiouscomplications of central venous catheters.JAMA 1994; 271:
10141016.
39. Lee AY, Levine MN, Butler G, et al. Incidence, risk factors,
and outcomes of catheter-related thrombosis in adult patients
with cancer.J Clin Oncol2006; 24: 14041408.
40. Luciani A, Clement O, Halimi P, et al. Catheter-related upper
extremity deep venous thrombosis in cancer patients: a pro-
spective study based on Doppler US. Radiology 2001; 220:
655660.
41. Tesselaar ME, Ouwerkerk J, Nooy MA, Rosendaal FR,
Osanto S. Risk factors for catheter-related thrombosis in can-
cer patients.Eur J Cancer2004; 40: 22532259.
42. Flinterman LE, van Hylckama Vlieg A, Rosendaal FR,
Doggen CJ. Recurrent thrombosis and survival after a first
venous thrombosis of the upper extremity. Circulation 2008;
118: 13661372.
43. Rodrigues CA, Ferrarotto R, Filho RK, Novis YA, Hoff PM.
Venous thromboembolism and cancer: a systematic review.
J Thromb Thrombolysis 2010; 30: 6778.
44. Zangari M, Fink LM, Elice F, Zhan F, Adcock DM, Tricot
GJ. Thrombotic events in patients with cancer receiving
antiangiogenesis agents.J Clin Oncol2009; 27: 48654873.
45. Bennett CL, Silver SM, Djulbegovic B, et al. Venous
thromboembolism and mortality associated with recom-
binant erythropoietin and darbepoetin administration for thetreatment of cancer-associated anemia. JAMA 2008; 299:
914924.
46. Vaya A, Mira Y, Ferrando F, Corella D, Aznar J. Does obesity
constitute a risk factor for upper-extremity deep vein throm-
bosis? Thromb Haemost2005; 94: 228230.
47. Chan WS, Ginsberg JS. A review of upper extremity deep
vein thrombosis in pregnancy: unmasking the ART behind
the clot.J Thromb Haemost2006; 4: 16731677.
48. Bauersachs RM, Manolopoulos K, Hoppe I, Arin MJ,
Schleussner E. More on: the ART behind the clot: solving
the mystery.J Thromb Haemost2007; 5: 438439.
49. Lindblad B, Tengborn L, Bergqvist D. Deep vein thrombosisof the axillary-subclavian veins: epidemiologic data, effects
of different types of treatment and late sequelae. Eur J Vasc
Surg1988; 2: 161165.
at Cairo University on September 6, 2011vmj.sagepub.comDownloaded from
http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/8/3/2019 Upper Extremity Deep Venous Thrombosis (2)
12/13
CzihalMandHoffmannU 201
50. Rooden CJ, Tesselaar ME, Osanto S, Rosendaal FR, Huisman
MV. Deep vein thrombosis associated with central venous
catheters a review.J Thromb Haemost2005; 3: 24092419.
51. Demondion X, Herbinet P, Van Sint JS, Boutry N, Chantelot
C, Cotten A. Imaging assessment of thoracic outlet syn-
drome.Radiographics 2006; 26: 17351750.
52. Kahn SR, Elman EA, Bornais C, Blostein M, Wells PS. Post-
thrombotic syndrome, functional disability and quality of
life after upper extremity deep venous thrombosis in adults.
Thromb Haemost2005; 93: 499502.
53. Elman EE, Kahn SR. The post-thrombotic syndrome after
upper extremity deep venous thrombosis in adults: a system-
atic review. Thromb Res 2006; 117: 609614.
54. Sabeti S, Schillinger M, Mlekusch W, Haumer M, Ahmadi
R, Minar E. Treatment of subclavian-axillary vein thrombo-
sis: long-term outcome of anticoagulation versus systemic
thrombolysis. Thromb Res 2002; 108: 279285.
55. Prandoni P, Bernardi E, Marchiori A, et al. The long term
clinical course of acute deep vein thrombosis of the arm: pro-spective cohort study.BMJ2004; 329: 484485.
56. Jones MA, Lee DY, Segall JA, et al. Characterizing reso-
lution of catheter-associated upper extremity deep venous
thrombosis.J Vasc Surg2010; 51: 108113.
57. Monreal M, Raventos A, Lerma R, et al. Pulmonary embolism in
patients with upper extremity DVT associated to venous central
linesa prospective study. Thromb Haemost1994; 72: 548550.
58. Baarslag HJ, Koopman MM, Hutten BA, et al. Long-term
follow-up of patients with suspected deep vein thrombosis
of the upper extremity: survival, risk factors and post-throm-
botic syndrome.Eur J Intern Med2004; 15: 503507.
59. Constans J, Salmi LR, Sevestre-Pietri MA, et al. A clinical
prediction score for upper extremity deep venous thrombo-
sis. Thromb Haemost2008; 99: 202207.
60. Di Nisio M, van Sluis GL, Bossuyt PM, Buller HR, Porreca
E, Rutjes AW. Accuracy of diagnostic tests for clinically sus-
pected upper extremity deep vein thrombosis: a systematic
review.J Thromb Haemost2010; 8: 684692.
61. Merminod T, Pellicciotta S, Bounameaux H. Limited useful-
ness of D-dimer in suspected deep vein thrombosis of the upper
extremities.Blood Coagul Fibrinolysis 2006; 17: 225226.
62. Chin EE, Zimmerman PT, Grant EG. Sonographic evaluation
of upper extremity deep venous thrombosis. J Ultrasound
Med2005; 24: 829838.
63. Patel MC, Berman LH, Moss HA, McPherson SJ. Subclavianand internal jugular veins at Doppler US: abnormal cardiac
pulsatility and respiratory phasicity as a predictor of com-
plete central occlusion.Radiology 1999; 211: 579583.
64. Baarslag HJ, van Beek EJ, Koopman MM, Reekers JA.
Prospective study of color duplex ultrasonography compared
with contrast venography in patients suspected of having
deep venous thrombosis of the upper extremities.Ann Intern
Med2002; 136: 865872.
65. Mustafa BO, Rathbun SW, Whitsett TL, Raskob GE.
Sensitivity and specificity of ultrasonography in the diagno-
sis of upper extremity deep vein thrombosis: a systematic
review.Arch Intern Med2002; 162: 401404.66. Hartnell GG, Hughes LA, Finn JP, Longmaid HE III.
Magnetic resonance angiography of the central chest veins.
A new gold standard? Chest1995; 107: 10531057.
67. Kroencke TJ, Taupitz M, Arnold R, Fritsche L, Hamm B.
Three-dimensional gadolinium-enhanced magnetic reso-
nance venography in suspected thrombo-occlusive disease
of the central chest veins. Chest2001; 120: 15701576.
68. Baarslag HJ, van Beek EJ, Reekers JA. Magnetic resonance
venography in consecutive patients with suspected deep vein
thrombosis of the upper extremity: initial experience. Acta
Radiol2004; 45: 3843.
69. Spiezia L, Simioni P. Upper extremity deep vein thrombosis.
Intern Emerg Med2010; 5: 103109.
70. Hoffmann U, Spannagl M. Deep venous thrombosis of the
upper extremity: is thrombophilia a relevant clinical issue?
Thromb Haemost2008; 100: 369370.
71. Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt
BJ, Hughes GR. The management of thrombosis in the anti-
phospholipid-antibody syndrome.N Engl J Med1995; 332:
993997.
72. Rosove MH, Brewer PM. Antiphospholipid thrombosis:
clinical course after the first thrombotic event in 70 patients.Ann Intern Med1992; 117: 303308.
73. Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T,
Rodger MA. Systematic review: the Trousseau syndrome
revisited: should we screen extensively for cancer in patients
with venous thromboembolism?Ann Intern Med2008; 149:
323333.
74. Savage KJ, Wells PS, Schulz V, et al. Outpatient use of low
molecular weight heparin (Dalteparin) for the treatment
of deep vein thrombosis of the upper extremity. Thromb
Haemost1999; 82: 10081010.
75. Kovacs MJ, Kahn SR, Rodger M, et al. A pilot study of cen-
tral venous catheter survival in cancer patients using low-
molecular-weight heparin (dalteparin) and warfarin without
catheter removal for the treatment of upper extremity deep
vein thrombosis (The Catheter Study). J Thromb Haemost
2007; 5: 16501653.
76. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob
GE, Comerota AJ; American College of Chest Physicians.
Antithrombotic therapy for venous thromboembolic disease:
American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest2008; 133(6
suppl): 454S545S.
77. Lee AY. Anti-thrombotic therapy in cancer patients. Expert
Opin Pharmacother2003; 4: 22132220.
78. Louzada ML, Majeed H, Wells PS. Efficacy of low-molec-ular-weight-heparin versus vitamin K antagonists for long
term treatment of cancer-associated venous thromboembo-
lism in adults: a systematic review of randomized controlled
trials. Thromb Res 2009; 123: 837844.
79. Thomas IH, Zierler BK. An integrative review of outcomes
in patients with acute primary upper extremity deep venous
thrombosis following no treatment or treatment with anti-
coagulation, thrombolysis, or surgical algorithms. Vasc
Endovascular Surg2005; 39: 163174.
80. Ponec D, Irwin D, Haire WD, Hill PA, Li X, McCluskey ER.
Recombinant tissue plasminogen activator (alteplase) for res-
toration of flow in occluded central venous access devices:a double-blind placebo-controlled trialthe Cardiovascular
Thrombolytic to Open Occluded Lines (COOL) efficacy
trial.J Vasc Interv Radiol2001; 12: 951955.
at Cairo University on September 6, 2011vmj.sagepub.comDownloaded from
http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/http://vmj.sagepub.com/8/3/2019 Upper Extremity Deep Venous Thrombosis (2)
13/13
202 VascularMedicine16(3)
81. Couban S, Goodyear M, Burnell M, et al. Randomized
placebo-controlled study of low-dose warfarin for the pre-
vention of central venous catheter-associated thrombosis in
patients with cancer.J Clin Oncol2005; 23: 40634069.
82. Young AM, Billingham LJ, Begum G, et al. Warfarin throm-
boprophylaxis in cancer patients with central venous cath-
eters (WARP): an open-label randomised trial.Lancet2009;
373: 567574.
83. Verso M, Agnelli G, Bertoglio S, et al. Enoxaparin for the pre-
vention of venous thromboembolism associated with central
vein catheter: a double-blind, placebo-controlled, randomized
study in cancer patients.J Clin Oncol2005; 23: 40574062.
84. Karthaus M, Kretzschmar A, Kroning H, et al. Dalteparin
for prevention of catheter-related complications in can-
cer patients with central venous catheters: final results of a
double-blind, placebo-controlled phase III trial. Ann Oncol
2006; 17: 289296.
85. Akl EA, Kamath G, Yosuico V, et al. Thromboprophylaxis
for patients with cancer and central venous catheters: a
systematic review and a meta-analysis. Cancer 2008; 112:
24832492.
86. Carrier M, Tay J, Fergusson D, Wells PS. Thromboprophylaxis
for catheter-related thrombosis in patients with cancer: a sys-
tematic review of the randomized, controlled trials.J Thromb
Haemost2007; 5: 25522554.
87. Chaukiyal P, Nautiyal A, Radhakrishnan S, Singh S,
Navaneethan SD. Thromboprophylaxis in cancer patients
with central venous catheters. A systematic review and meta-
analysis. Thromb Haemost2008; 99: 3843.
88. Geerts WH, Bergqvist D, Pineo GF, et al.; American College
of Chest Physicians. Prevention of venous thromboembo-
lism: American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest 2008;
133(6 suppl): 381S453S.